雷奈酸锶防治骨质疏松相关邻近节段椎间盘退变及通过基质代谢与生物力学介导的机制研究

Lumbar fusion is one of the most commonly performed lumbar surgeries, its long-term clinical efficacy has not been improved, mainly due to the high incidence of adjacent segment disc degeneration (ASDD). Postmenopausal osteoporosis (POP) is characterized by low bone mass, deterioration of bone tissue, and high incidence of fracture. Here are increasing evidence that low levels of vertebral BMD accelerate or result in disc degeneration and ASDD. Strontium strontium is a new-generation of anti-osteoporosis drugs, it's biggest characteristic is to promote bone formation and inhibit bone resorption. Our previous studies have demonstrated that anti-osteoporosis drugs are effective in relieving ASDD in osteopenia. Furthermore, the literature confirmed that strontium ranelate can promote cartilage matrix formation and subchondral bone remodeling. These findings indicate that Strontium strontium has potential effect on delaying osteoporosis-associated ASDD, but its mechanism on the tissue and molecular level needs to be further studied. Therefore, we choose Strontium ranelate as an intervention to reveal the changes resulting from the unbalanced metabolism of disc and endplate and clarify the relationships among the changes of disc structure and mechanics, disc and endplate metabolism, using histomorphology, bone histomorphometry, biomechanics and molecular biology assessment, and finally to provide a potential option for ASDD treatment in osteopenia in future.

脊柱融合术是脊柱外科常用的术式之一，其远期疗效并没有得到提高，主要是因为发生了邻近节段椎间盘退变（ASDD）。绝经后骨质疏松（POP）是一类由雌激素缺乏导致骨量减少及骨微结构改变，骨脆性增加易于骨折的疾病。有证据表明骨质疏松可以加速ASDD，表明POP影响脊柱融合的预后。雷奈酸锶（SR）是新型的抗骨质疏松药，最大特点在于同时具有促进骨形成并抑制骨吸收作用。之前的研究已证实，抗骨质疏松药物可以有效的缓解POP相关ASDD。文献报道SR可以促进软骨基质形成及软骨下骨重建。这些证据表明SR具有潜在的延缓POP相关ASDD的功能，其在组织与分子水平的作用机制有待深入研究。因此本实验通过组织形态学、骨形态计量学、分子生物学以及生物力学等手段，拟进一步揭示POP、基质代谢失衡及结构损害所造成ASDD的机制，明确SR延缓POP相关ASDD的作用机制，为临床预防及治疗POP相关ASDD提供选择。

本实验按照原先计划的方式建立骨质疏松大鼠脊柱融合后邻近节段椎间盘退变模型，并通过给予口饲雷奈酸锶干混剂，在改善其骨质疏松的前提下，观察其是否能够改善脊柱融合后邻近节段椎间盘退变，同时我们应用各种方法，例如组织形态学、影像学以及分子生物学，对其潜在的机制进行初步探索，为临床治疗骨质疏松患者脊柱融合后邻近节段椎间盘退变提供理论依据及临床用药指导。 本实验通过对邻近节段椎体、终板以及椎间盘的分析，并通过进行Micro-CT、组织学的微血管数量及面积分析、免疫组织化学以及RT-PCR实验来试图阐述卵巢切除大鼠ASDD的发病机理及雷奈酸锶延缓卵巢切除大鼠ASDD的作用机制。其作用机制可能与维持椎体及软骨终板结构和功能的完整性有关。同时，雷奈酸锶可以通过调节Col-I、Co1-II、蛋白多糖、MMP-13以及ADAMTS-4的表达，影响椎间盘基质的代谢。因此，雷奈酸锶是一种可以预防与骨质疏松相关的ASDD的潜在性药物。